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Colorectal cancer (CRC) is a major health burden worldwide due to its high morbidity, mortality, and complex etiology. Fusobacterium nucleatum (Fn), a Gram-negative anaerobe found in 30% of CRC patients, promotes CRC carcinogenesis, metastasis, and chemoresistance. Effective antimicrobial treatment is an unmet need for the rising CRC burden. Antimicrobial peptides (AMPs) represent a new class of antimicrobial drugs. In our previous study, we did the structure-activity study of Jelleine-I (J-I) and identified several halogenated J-I derivatives Cl-J-I, Br-J-I, and I-J-I. To determine whether those J-I derivatives can be a new therapy for bacterial-associated CRC, here we tested the antibacterial activities of these AMPs against Fn and their effects on CRC development. We found that Br-J-I showed the highest anti-Fnactivity and Br-J-I may target membrane-associated FadA for Fn membrane disruption. More importantly, Fn promoted the growth of CRC cells-derived xenograft tumors. Br-J-I suppressed Fn load, colon inflammation, and Fn-induced CRC growth. Of note, Br-J-I induced better anti-CRC effects than common antibiotic metronidazole and Br-J-I sensitized the cancer-killing effect of chemotherapy drug 5-fluorouracil. These results suggest that Br-J-I could be considered as an adjunctive agent for CRC treatment and AMPs-based combination treatment is a new strategy for CRC in the future.

Free radical polymerization of styrene in supercritical CO 2 requires addition of a surfactant to produce polystyrene (PS) in high conversion and molecular weight with well-defined particle sizes. In this work, we examined a new stabilizer that can provide effective stabilization for the polymerization of styrene. A commercially available poly(dimethylsiloxane) macromonomer has been employed as a stabilizer for dispersion polymerization of PS in scCO 2 . The reactions were conducted in a 225-mL stainless steel autoclave over the temperature range 60 -80°C and under pressures of 1,500 to 3,000 psi. After 2-12 h of polymerization, the conversion determined by gravimetrical method was between 20 and 80%. These preliminary results suggest that this macromonomer offers satisfactory stabilization for the styrene system.

The imbalance between reactive oxygen species (ROS) production and clearance causes oxidative stress and ROS, which play a central role in regulating cell and tissue physiology and pathology. Contingent upon concentration, ROS influence cancer development in contradictory ways, either stimulating cancer survival and growth or causing cell death. Cells developed evolutionarily conserved programs to sense and adapt redox the fluctuations to regulate ROS as either signaling molecules or toxic insults. The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2)-KEAP1 system is the master regulator of cellular redox and metabolic homeostasis. NRF2 has Janus-like roles in carcinogenesis and cancer development. Short-term NRF2 activation suppresses tissue injury, inflammation, and cancer initiation. However, cancer cells often exhibit constitutive NRF2 activation due to genetic mutations or oncogenic signaling, conferring advantages for cancer cells’ survival and growth. Emerging evidence suggests that NRF2 hyperactivation, as an adaptive cancer phenotype under stressful tumor environments, regulates all hallmarks of cancer. In this review, we summarized the source of ROS, regulation of ROS signaling, and cellular sensors for ROS and oxygen (O2), we reviewed recent progress on the regulation of ROS generation and NRF2 signaling with a focus on the new functions of NRF2 in cancer development that reach beyond what we originally envisioned, including regulation of cancer metabolism, autophagy, macropinocytosis, unfolded protein response, proteostasis, and circadian rhythm, which, together with anti-oxidant and drug detoxification enzymes, contributes to cancer development, metastasis, and anticancer therapy resistance.

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